Recombinant Erythropoietin for Neuroprotection in Very Preterm Infants

NCT00910234 | Unknown Phase 1 DMC

• 1 other identifier: DMR-98
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Periventricular leukomalacia (PVL) is one of the most common brain injuries that occur in preterm infants. Inflammation, hypoxia-ischemia, free oxygen radical formation and excitotoxicity are all known pathogenic mechanisms that mediate this injury. Erythropoietin (EPO) has been shown to be protective against hypoxic-ischemic and inflammatory injuries. During the past decade, recombinant human Epo (rhEpo) has been widely used in preterm infants to prevent or treat the anemia of prematurity, in general, rhEpo has been considered to be safe and well tolerated in preterm infants. EPO was considered not capable of passing through blood-brain-barrier at low dose. Evidence from animal experiments reveals that rhEpo must be given in high doses at the beginning or within a short (up to 6 hours), critical time period after the onset of brain injury to achieve a significant neuroprotective effect. A recent study using high-dose rhEpo (3000 U rhEpo/kg body weight at birth) for neuroprotection in very preterm infants revealed that no signs of adverse effects of early high-dose rhEpo treatment in very preterm infants were identified. Contrary to this, a recent study in PVL of a rat model revealed that using a low dose rhEpo (50-100 U/kg) was effective in the treatment of brain damage induced by hypoxia-ischemia and did not affect normal oligodendrocyte maturity. On this basis, the researchers intent to investigate (1) whether low-dose rhEpo (100 U/kg) or high-dose rhEpo (3,000 U/kg) given to very preterm infants (gestation age \< 32 weeks) immediately after birth and subsequently during the first 2 days is safe and possesses neuroprotective properties;(2) whether there are gender differences in response to the hypoxia-ischemic insult and EPO treatment; (3)the pharmacokinetics of low dose and high dose rhEPO. Very preterm infants with gestational age of \< 32 weeks and admitted to the NICU are eligible for enrollment.

Conditions

Infant, Premature; Leukomalacia, Periventricular; Intraventricular Hemorrhage; Retinopathy of Prematurity

Keywords

Periventricular leukomalacia (PVL); Erythropoietin (EPO); Retinopathy of prematurity (ROP); Hypoxia-ischemia

Outcome Measures

Primary Outcomes (1)

• The primary short-term outcome measures are brain injury (intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL)) and ROP.

  2 months

Secondary Outcomes (1)

• The secondary outcomes are sepsis, necrotizing enterocolitis (NEC), persistent ductus arteriosus (PDA), apnea of prematurity, and chronic lung disease.

  2 months

Study Arms (3)

Drug: rhEpo, low dose

ACTIVE COMPARATOR

rhEpo is administered 100 U/kg, iv at 3 to 6 hours after birth, and at 24 hours interval for another 2 doses.

Drug: recombinant human erythropoietin (rhEpo)

Drug: rhEpo, high dose

ACTIVE COMPARATOR

rhEpo is administered 3000 U/kg, iv at 3 to 6 hours after birth, and at 24 hours interval for another 2 doses.

Drug: recombinant human erythropoietin (rhEpo)

Control Normal saline

PLACEBO COMPARATOR

normal saline is administered 0.5/kg, iv at 3 to 6 hours after birth, and at 24 hours interval for another 2 doses.

Drug: Normal saline

Interventions

recombinant human erythropoietin (rhEpo) DRUG

rhEpo is administered 3000 U/kg, iv at 3 to 6 hours after birth, and at 24 hours interval for another 2 doses.

Also known as: Epoietin Beta

Drug: rhEpo, high dose

Normal saline DRUG

normal saline is administered 0.5/kg, iv at 3 to 6 hours after birth, and at 24 hours interval for another 2 doses.

Also known as: N/S solution

Control Normal saline

Eligibility Criteria

• Age: 2 Hours - 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• After informed consent is obtained, very preterm infants with gestational age of \< 32 weeks and admit to our NICU are eligible for enrollment.

You may not qualify if:

• Genetically defined syndromes,
• Congenital malformations that adversely affect neurodevelopment.

Sponsors & Collaborators

• China Medical University Hospital: lead

Study Sites (1)

China Medical University Hospital

Taichung, 400, Taiwan

Location

MeSH Terms

Conditions

Premature Birth; Leukomalacia, Periventricular; Retinopathy of Prematurity

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Encephalomalacia; Vascular Diseases; Cardiovascular Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Bai-Horng Su, MD, PhD

  China Medical University Hospital

  STUDY CHAIR

Central Study Contacts

Bai-Horng Su, MD, PhD

CONTACT

886-4-22052121; bais@ms49.hinet.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 28, 2009
• First Posted: May 29, 2009
• Study Start: August 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: May 29, 2009

Record last verified: 2009-05

Locations

TW (1)